• Title/Summary/Keyword: circulating tumor cell

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Diagnostic Yield of Primary Circulating Tumor Cells in Women Suspected of Breast Cancer: the BEST (Breast Early Screening Test) Study

  • Murray, Nigel P;Miranda, Roxana;Ruiz, Amparo;Droguett, Elsa
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1929-1934
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    • 2015
  • Purpose: To determine the diagnostic yield of primary circulating tumor cells in women with suspicion of breast cancer, detected as a result of an abnormal mammography. Materials and Methods: Consecutive women presenting for breast biopsy as a result of a mammogram BiRADs of 3 or more, had an 8ml blood sample taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were obtained using differential gel centrifugation and CTCs identified using standard immunocytochemistry using anti-mammoglobin. A test was determined to be positive if 1 CTC was detected. Results: A total of 144 women with a mean age of $54.7{\pm}15.6$ years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140 (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24, 8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of 90.9%, with positive and negative predictive values of 90.9% and 81.1% respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ cancers and none of the intraductal cancers had CTCs detected. Menopausal status did not affect the diagnostic yield of the CTC test, which was higher in women with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for trends) in CTC detection frequency from intraductal, in situ and invasive (OR 1.00, 8.00, 472.00). Conclusions: The use of primary CTC detection in women suspected of breast cancer has potential uses, especially with invasive cancer, but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was no difference in the diagnostic yield between pre and post menopausal women. To confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in the detection of interval invasive breast cancer, larger studies are needed.

Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer

  • Heo, Jaesung;Oh, Young-Taek;Noh, O Kyu;Chun, Mison;Park, Jun-Eun;Cho, Sung-Ran
    • Radiation Oncology Journal
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    • v.34 no.4
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    • pp.305-312
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    • 2016
  • Purpose: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count - cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

Microchips and their Significance in Isolation of Circulating Tumor Cells and Monitoring of Cancers

  • Sahmani, Mehdi;Vatanmakanian, Mousa;Goudarzi, Mehdi;Mobarra, Naser;Azad, Mehdi
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.879-894
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    • 2016
  • In micro-fluid systems, fluids are injected into extremely narrow polymer channels in small amounts such as micro-, nano-, or pico-liter scales. These channels themselves are embedded on tiny chips. Various specialized structures in the chips including pumps, valves, and channels allow the chips to accept different types of fluids to be entered the channel and along with flowing through the channels, exert their effects in the framework of different reactions. The chips are generally crystal, silicon, or elastomer in texture. These highly organized structures are equipped with discharging channels through which products as well as wastes of the reactions are secreted out. A particular advantage regarding the use of fluids in micro-scales over macro-scales lies in the fact that these fluids are much better processed in the chips when they applied as micro-scales. When the laboratory is miniaturized as a microchip and solutions are injected on a micro-scale, this combination makes a specialized construction referred to as "lab-on-chip". Taken together, micro-fluids are among the novel technologies which further than declining the costs; enhancing the test repeatability, sensitivity, accuracy, and speed; are emerged as widespread technology in laboratory diagnosis. They can be utilized for monitoring a wide spectrum of biological disorders including different types of cancers. When these microchips are used for cancer monitoring, circulatory tumor cells play a fundamental role.

Serum Level of MMP-3 in Patients with Oral Squamous Cell Carcinoma - Lack of Association with Clinico-pathological Features

  • Tadbir, Azadeh Andisheh;Purshahidi, Sara;Ebrahimi, Hooman;Khademi, Bijan;Malekzadeh, Mahzad;Mardani, Maryam;Taghva, Masumeh;Sardari, Yasaman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4545-4548
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    • 2012
  • Background: MMP-3 is a proteolytic enzyme of the matrix metalloproteinase family. Protein degradation which is their fundamental action regulates different activities of tumor cell such as their growth, differentiation, apoptosis, migration, invasion, angiogenesis as well as their resistance to the immune system. Aim: The aim of this study was to determine MMP-3 serum levels in patients with OSCC and investigate if they correlate with clinicopathological features. Method and materials: Using an ELISA kit, we assessed and compared the circulating levels of MMP-3 in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. Results: The serum MMP-3 level in OSCC patients was significantly higher ($9.45{\pm}4.6$ ng/ml) than healthy controls ($5.9{\pm}3.6$ ng/ml, p<0.001), especially in females and in older patients. However, there was no apparent correlation in serum MMP-3 concentration with the clinico-pathological features such as tumor location, stage, tumor size, nodal status, distant metastasis, histological grade and smoking. Discussion: This result suggests that the measurement of serum MMP-3 concentration might be helpful to diagnose OSCC but not to predict prognosis.

Matrix Metalloproteinase-13 - A Potential Biomarker for Detection and Prognostic Assessment of Patients with Esophageal Squamous Cell Carcinoma

  • Sedighi, Maryam;Aledavood, Seyed Amir;Abbaszadegan, MR;Memar, Bahram;Montazer, Mehdi;Rajabian, Majid;Gholamin, Mehran
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2781-2785
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    • 2016
  • Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

Serum Level of Mast Cell Tryptase in Patients with Oral Squamous Cell Carcinoma: Lack of Correlation with Clinicopathologic Factors

  • Jaafari-Ashkavandi, Zohreh;Khademi, Bijan;Akbari, Somayeh;Malekzadeh, Mahyar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2955-2958
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    • 2013
  • Background: Mast cells can influence tumor progression via different pathways and increased mast cell density has been demonstrated in oral squamous cell carcinoma (OSCC). It has been shown that the serum tryptase level is elevated with some malignant tumours and may thus be a useful parameter. However, there are no data available about OSCC. The main aim of this study was the evaluation of mast cell tryptase (MCT) level in OSCC patient serum. Materials and Methods: In this cross-sectional, analytic study, the circulating levels of MCT were assessed in sera of 55 OSCC patients and 34 healthy individuals with ELISA technique. Results: The serum MCT level in OSCC patients was 12-14 ng/ml, which was not significantly higher than the healthy control group. While the serum level of MCT was higher with larger tumours, there was no apparent correlation with clinico-pathological features such as patient age, gender, tumor location, stage, nodal status, distant metastasis, histological grade and smoking. Conclusions: Our findings showed that despite the results obtained from studies of other malignant tumors, serum level of MCT in OSCC patients could not be a credited as a reliable indicator of the presence or progression of tumours.

Phloroglucinol Inhibits the in vitro Differentiation Potential of CD34 Positive Cells into Endothelial Progenitor Cells

  • Kwon, Yi-Hong;Lee, Jun-Hee;Jung, Seok-Yun;Kim, Jae-Won;Lee, Sang-Hun;Lee, Dong-Hyung;Lee, Kyu-Sup;Lee, Boo-Yong;Kwon, Sang-Mo
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.158-164
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    • 2012
  • Inhibiting the bioactivities of circulating endothelial progenitor cells (EPCs) results in significant inhibition of neovessel formation during tumor angiogenesis. To investigate the potential effect of phloroglucinol as an EPC inhibitor, we performed several in vitro functional assays using $CD34^+$ cells isolated from human umbilical cord blood (HUCB). Although a high treatment dose of phloroglucinol did not show any cell toxicity, it specifically induced the cell death of EPCs under serum free conditions through apoptosis. In the EPC colony-forming assay (EPC-CFA), we observed a significant decreased in the small EPC-CFUs for the phloroglucinol group, implying that phloroglucinol inhibited the early stage of EPC commitment. In addition, in the in vitro expansion assay using $CD34^+$ cells, treatment with phloroglucinol was shown to inhibit endothelial lineage commitment, as demonstrated by the decrease in endothelial surface markers of EPCs including $CD34^+$, $CD34^+/CD133^+$, $CD34^+/CD31^+$ and $CD34^+/CXCR4^+$. This is the first report to demonstrate that phloroglucinol can inhibit the functional bioactivities of EPCs, indicating that phloroglucinol may be used as an EPC inhibitor in the development of biosafe anti-tumor drugs that target tumor angiogenesis.

Serum IL-33 as a Diagnostic and Prognostic Marker in Non-small Cell Lung Cancer

  • Hu, Liang-An;Fu, Yu;Zhang, Dan-Ni;Zhang, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2563-2566
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    • 2013
  • Background: Interleukin-33 (IL-33) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of serum IL-33 in patients with non-small-cell lung cancer (NSCLC). Methods: Sera collected from 250 healthy volunteers (HV), 256 patients with benign lung diseases (BLD) and 262 NSCLC cases were subjected to IL-33 ELISA and relationships between serum IL-33 and clinical characteristics were evaluated. Results: Circulating IL-33 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). Using a cut-off level 68 pg/ml (95% specificity in the HV group), IL-33 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that serum IL-33 was an independent prognostic factor in the entire NSCLC group [hazards ratio (HR) = 0.64 for low versus high IL-33 levels, 95% confidence interval (CI) 0.50-0.82; p<0.001] and in 165 selected patients with locally advanced or metastatic disease receiving chemoradiotherapy or chemotherapy (HR 0.70, 95% CI 0.52-0.94; p=0.013). Conclusions: IL-33 is a promising potential diagnostic and prognostic marker in NSCLC, independent of the therapeutic intervention.

Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils

  • Wang, Xinbo;Tang, Mingyu;Zhang, Yuming;Li, Yansong;Mao, Jingdong;Deng, Qinghua;Li, Shusen;Jia, Zhenwei;Du, Liyin
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.76.1-76.14
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    • 2022
  • Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

T-plastin contributes to epithelial-mesenchymal transition in human lung cancer cells through FAK/AKT/Slug axis signaling pathway

  • Soon Yong Park;Hyeongrok Choi;Soo Min Choi;Seungwon Wang;Sangin Shim;Woojin Jun;Jungkwan Lee;Jin Woong Chung
    • BMB Reports
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    • v.57 no.6
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    • pp.305-310
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    • 2024
  • T-plastin (PLST), a member of the actin-bundling protein family, plays crucial roles in cytoskeletal structure, regulation, and motility. Studies have shown that the plastin family is associated with the malignant characteristics of cancer, such as circulating tumor cells and metastasis, by inducing epithelial-mesenchymal transition (EMT) in various cancer cells. However, the role of PLST in the EMT of human lung cancer cells remains unclear. In this study, we observed that PLST overexpression enhanced cell migratory and invasive abilities, whereas its downregulation resulted in their suppression. Moreover, PLST expression levels were associated with the expression patterns of EMT markers, including E-cadherin, vimentin, and Slug. Furthermore, the phosphorylation levels of focal adhesion kinase (FAK) and AKT serine/threonine kinase (AKT) were dependent on PLST expression levels. These findings indicate that PLST induces the migration and invasion of human lung cancer cells by promoting Slug-mediated EMT via the FAK/AKT signaling pathway.